Premium
Analysis of RYR1 Haplotype Profile in Patients with Malignant Hyperthermia
Author(s) -
Carpenter D.,
Morris A.,
Robinson R. L.,
Booms P.,
Iles D.,
Halsall P. J.,
Steele D.,
Hopkins P. M.,
Shaw M.A.
Publication year - 2009
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2008.00482.x
Subject(s) - haplotype , ryr1 , malignant hyperthermia , population , snp , genetic association , genetics , biology , single nucleotide polymorphism , genotype , medicine , gene , pathology , environmental health , ryanodine receptor , intracellular
Summary This study represents a new approach to characterising patients at risk of malignant hyperthermia (MH) through the use of a recently published method for identifying high‐risk haplotypes in candidate genes. We present analysis based upon the largest standardised and genotyped database of MH patients worldwide. We used unphased RYR1 SNP data directly to (1) assess RYR1 haplotype frequency differences between susceptible cases and control groups and (2) analyse population‐based association via clustering of RYR1 haplotypes based on disease risk. Our results show a significant difference in RYR1 haplotype frequency between susceptible cases and UK Caucasian population controls. Furthermore we identify a high‐risk cluster of haplotypes that is associated with the commonest UK MH mutation p.G2434R/c.7300G>A. These results demonstrate the applicability of this new and practical method for population based association analysis.